Phenotypes associated with this allele

• Allele Symbol: Ercc2^{tm2(ERCC2)Jhjh}
• Allele Name: targeted mutation 2, Jan H J Hoeijmakers
• Allele ID: MGI:2183949
• Summary: 8 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ercc2^tm2(ERCC2)Jhjh/Ercc2^tm2(ERCC2)Jhjh	involves: 129P2/OlaHsd	MGI:3836476
hm2	Ercc2^tm2(ERCC2)Jhjh/Ercc2^tm2(ERCC2)Jhjh	involves: 129P2/OlaHsd * C57BL/6	MGI:2386444
ht3	Ercc2^tm1Jhjh/Ercc2^tm2(ERCC2)Jhjh	involves: 129P2/OlaHsd * C57BL/6	MGI:2386443
ht4	Ercc2^tm1Jmch/Ercc2^tm2(ERCC2)Jhjh	involves: 129P2/OlaHsd * C57BL/6	MGI:3696347
ht5	Ercc2^tm2(ERCC2)Jhjh/Ercc2^tm2Jmch	involves: 129P2/OlaHsd * C57BL/6	MGI:3696349
ht6	Ercc2^tm2(ERCC2)Jhjh/Ercc2^tm3Jhjh	involves: 129P2/OlaHsd * C57BL/6	MGI:3696355
cx7	Ercc2^tm2(ERCC2)Jhjh/Ercc2^tm2(ERCC2)Jhjh Xpa^tm1Hvs/Xpa^tm1Hvs	involves: 129P2/OlaHsd * C57BL/6	MGI:2386447
cx8	Ercc2^tm2(ERCC2)Jhjh/Ercc2^tm2(ERCC2)Jhjh Ercc3^tm2Jhjh/Ercc3^tm2Jhjh	involves: 129P2/OlaHsd * C57BL/6	MGI:3836475

Genotype
MGI:3836476

hm1

• Allelic Composition: Ercc2^{tm2(ERCC2)Jhjh}/Ercc2^{tm2(ERCC2)Jhjh}
• Genetic Background: involves: 129P2/OlaHsd

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

cellular

increased cellular sensitivity to ultraviolet irradiation ( J:145759 )

• mild

immune system

immune system phenotype ( J:47993 )

N • somatic hypermutation rates in memory B cells are normal

Genotype
MGI:2386444

hm2

• Allelic Composition: Ercc2^{tm2(ERCC2)Jhjh}/Ercc2^{tm2(ERCC2)Jhjh}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

Cutaneous phenotypes of Ercc2^{tm2(ERCC2)Jhjh}/Ercc2^{tm2(ERCC2)Jhjh} and Ercc2^{tm2(ERCC2)Jhjh}/Ercc2^tm2Jmch mice

mortality/aging

premature death ( J:48256 , J:116054 )

• most dead by 1 year (J:48256)

premature aging ( J:76608 )

• acquire an aged appearance beginning at 3 months of age

neoplasm

neoplasm ( J:112689 )

N • no sign of cancer predisposition after exposure to a daily dose of 80 J/m² UV

increased incidence of induced tumors ( J:48256 )

• increased UV- and DMBA-induced skin cancer susceptibility

pigmentation

white spotting ( J:76608 )

• show patchy depigmentation earlier and more frequently than wild-type as they age

behavior/neurological

tremors ( J:48256 )

• occasional tremors, however no overt myelination defect

growth/size/body

cachexia ( J:48256 , J:76608 , J:116054 )

• progressive weight loss and cachexia as death neared (J:48256)

disproportionate dwarf ( J:48256 )

• cachectic dwarfism

postnatal growth retardation ( J:48256 , J:116054 )

• evident from birth (J:48256)

enlarged spleen ( J:76608 )

• progressive with age

hematopoietic system

enlarged spleen ( J:76608 )

• progressive with age

anemia ( J:76608 , J:116054 )

• mild normochrome anemia at 6 months of age (J:76608)

decreased erythrocyte cell number ( J:76608 )

• 84% of wild-type

decreased hematocrit ( J:76608 )

decreased hemoglobin content ( J:76608 )

immune system

enlarged spleen ( J:76608 )

• progressive with age

reproductive system

abnormal ovulation ( J:76608 )

♀ • older females (~16 months) showed ovarian dysfunction, ranging from complete anovulation to sporadic, seemingly normal, ovulation

reduced female fertility ( J:48256 , J:76608 )

♀ (J:48256)

♀ • females lose fertility over time, never produce more than one litter and never produce a litter after 6 months of age, although initial sexual development is unimpaired (J:76608)

skeleton

abnormal skeleton morphology ( J:48256 )

• showed signs of skeleton abnormalities

kyphosis ( J:76608 , J:116054 )

• prominently exhibited in older mice (14 months of age) (J:76608)

decreased bone mineral density ( J:76608 )

• reduced radiodensity of skeleton, except for skull, observed in older mice (14 months of age)

osteoporosis ( J:76608 , J:116054 )

adipose tissue

abnormal fat cell morphology ( J:48256 )

• adipose tissue hypoplasia, most prominent at older age

endocrine/exocrine glands

abnormal sebaceous gland morphology ( J:116054 )

enlarged sebaceous gland ( J:76608 )

• benign hyperplasia of the sebaceous gland

homeostasis/metabolism

abnormal circulating amino acid level ( J:76608 )

• decrease in serum levels of branched-chain amino acids (valine, leucine, and isoleucine) at 6 months of age, indicating starvation

cellular

abnormal cell physiology ( J:112689 )

• following UV exposure DNA incision activity and unscheduled DNA synthesis are decreased compared to wild-type MEFs

integument

abnormal sebaceous gland morphology ( J:116054 )

enlarged sebaceous gland ( J:76608 )

• benign hyperplasia of the sebaceous gland

abnormal coat/ hair morphology ( J:48256 )

• reduced cysteine content of hair and increased fraction of intermedaite filament keratins in hair

white spotting ( J:76608 )

• show patchy depigmentation earlier and more frequently than wild-type as they age

alopecia ( J:48256 )

• progressive hair loss, beginning at head around P19

• by 4 weeks of age, most hair absent, except a small band of fur at feet and tail

• mew coat grew with second cycle of hair growth, but progressive hair loss again followed

sparse hair ( J:116054 )

brittle hair ( J:48256 , J:116054 )

greasy coat ( J:48256 , J:116054 )

abnormal hair follicle morphology ( J:48256 )

• abnormal cuticle structure

enlarged hair follicles ( J:48256 )

• follicular plugging and dilation

hyperkeratosis ( J:48256 , J:116054 )

abnormal epidermis stratum granulosum morphology ( J:116054 )

• hyperplasia

acanthosis ( J:48256 , J:116054 )

• thickening of the granular layer (J:48256)

scaly skin ( J:48256 )

• ichthyosis, particularly in the neck region

thick skin ( J:48256 )

• ichthyosis, particulary in the neck region

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
photosensitive trichothiodystrophy		DOID:2960		J:48256 , J:76608

Genotype
MGI:2386443

ht3

• Allelic Composition: Ercc2^tm1Jhjh/Ercc2^{tm2(ERCC2)Jhjh}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

premature death ( J:48256 )

• most dead by 1 year

neoplasm

increased incidence of tumors by chemical induction ( J:48256 )

• increased DMBA-induced skin cancer susceptibility

increased skin tumor incidence ( J:48256 )

• increased UV- and DMBA-induced skin cancer susceptibility

increased incidence of tumors by UV-induction ( J:48256 )

• increased UV-induced skin cancer susceptibility

adipose tissue

decreased total body fat amount ( J:48256 )

• adipose tissue hypoplasia

behavior/neurological

tremors ( J:48256 )

growth/size/body

cachexia ( J:48256 )

• progressive weight loss and cachexia as death neared

postnatal growth retardation ( J:48256 )

• evident from birth

hematopoietic system

anemia ( J:48256 )

decreased erythrocyte cell number ( J:48256 )

• decreased RBC count

decreased hematocrit ( J:48256 )

abnormal hemoglobin ( J:48256 )

• decreased hemoglobin concentration

cellular

increased cellular sensitivity to ultraviolet irradiation ( J:116054 )

• increased sensitivity of MEFs to UV irradiation

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:48256 )

• increased DMBA-induced skin cancer susceptibility

integument

alopecia ( J:48256 )

• progressive hair loss, beginning at head ~P19

• by 4 weeks of age, most hair absent, except a small band of fur at feet and tail

• new coat grew with second cycle of hair growth, but progressive hair loss again followed

brittle hair ( J:48256 )

greasy coat ( J:48256 )

abnormal hair cuticle ( J:48256 )

• abnormal cuticle structure

abnormal hair follicle morphology ( J:48256 )

• follicular plugging and dilation

hyperkeratosis ( J:48256 )

acanthosis ( J:48256 )

scaly skin ( J:48256 )

• ichthyosis, particularly in the neck region

thick skin ( J:48256 )

• ichthyosis, particularly in the neck region

increased skin tumor incidence ( J:48256 )

• increased UV- and DMBA-induced skin cancer susceptibility

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
photosensitive trichothiodystrophy		DOID:2960		J:48256

Genotype
MGI:3696347

ht4

• Allelic Composition: Ercc2^tm1Jmch/Ercc2^{tm2(ERCC2)Jhjh}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

mortality/aging ( J:116054 )

N • normal lifespan unlike Ercc2^{tm2(ERCC2)Jhjh} homozygotes

cellular

decreased cellular sensitivity to ultraviolet irradiation ( J:116054 )

• UV sensitivity is less than in Ercc2^{tm2(ERCC2)Jhjh} Ercc2^tm1Jhjh compound heterozygotes

• decrease in UV sensitivity is not as large as in Ercc2^{tm2(ERCC2)Jhjh} Ercc2^tm2Jmch compound heterozygotes

growth/size/body

growth/size/body region phenotype ( J:116054 )

N • full rescue of age-related cachexia that is seen in Ercc2^{tm2(ERCC2)Jhjh} homozygotes

integument

focal dorsal hair loss ( J:116054 )

• only seen during the first hair cycle and only locally on the back

Genotype
MGI:3696349

ht5

• Allelic Composition: Ercc2^{tm2(ERCC2)Jhjh}/Ercc2^tm2Jmch
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

Cutaneous phenotypes of Ercc2^{tm2(ERCC2)Jhjh}/Ercc2^{tm2(ERCC2)Jhjh} and Ercc2^{tm2(ERCC2)Jhjh}/Ercc2^tm2Jmch mice

mortality/aging

mortality/aging ( J:116054 )

N • normal lifespan unlike Ercc2^{tm2(ERCC2)Jhjh} homozygotes

growth/size/body

growth/size/body region phenotype ( J:116054 )

N • full rescue of age-related cachexia that is seen in Ercc2^{tm2(ERCC2)Jhjh} homozygotes

postnatal growth retardation ( J:116054 )

• partial rescue of developmental delay compared to Ercc2^{tm2(ERCC2)Jhjh} homozygotes

hematopoietic system

anemia ( J:116054 )

• partially rescued compared to Ercc2^{tm2(ERCC2)Jhjh} homozygotes

skeleton

skeleton phenotype ( J:116054 )

N • mice do not develop osteoporosis or kyphosis any earlier than wild-type mice

cellular

decreased cellular sensitivity to ultraviolet irradiation ( J:116054 )

• UV sensitivity is less than in Ercc2^{tm2(ERCC2)Jhjh} homozygotes

integument

integument phenotype ( J:116054 )

N • absence of acanthosis, hyperkeratosis, and granular layer and sebacious gland hyperplasia

focal dorsal hair loss ( J:116054 )

• only seen during the first hair cycle and only locally on the back

brittle hair ( J:116054 )

• less severe than in Ercc2^{tm2(ERCC2)Jhjh} homozygotes

• only a very low frequency of broken hairs

Genotype
MGI:3696355

ht6

• Allelic Composition: Ercc2^{tm2(ERCC2)Jhjh}/Ercc2^tm3Jhjh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

integument

integument phenotype ( J:116054 )

N • normal hair morphology

Genotype
MGI:2386447

cx7

• Allelic Composition: Ercc2^{tm2(ERCC2)Jhjh}/Ercc2^{tm2(ERCC2)Jhjh}; Xpa^tm1Hvs/Xpa^tm1Hvs
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

neonatal lethality, incomplete penetrance ( J:76608 )

• incomplete penetrance

postnatal lethality, complete penetrance ( J:76608 )

• surviving mice dead by 22 days of age

premature aging ( J:76608 )

behavior/neurological

abnormal gait ( J:76608 )

growth/size/body

cachexia ( J:76608 )

• develop extreme cachexia by 2-3 weeks of age

postnatal growth retardation ( J:76608 )

• exhibit a retarded but steady growth until 1.5 weeks, but fail to gain weight after 2-3 weeks

skeleton

kyphosis ( J:76608 )

osteoporosis ( J:76608 )

adipose tissue

abnormal adipose tissue distribution ( J:76608 )

• complete absence of body fat, including subcutaneous fat

cellular

abnormal cell death ( J:76608 )

increased cellular sensitivity to X-ray irradiation ( J:76608 )

• seen in MEFs

increased cellular sensitivity to oxidative stress ( J:76608 )

increased cellular sensitivity to ultraviolet irradiation ( J:76608 )

integument

dilated hair follicle ( J:76608 )

• severe dilation of hair follicles

hyperkeratosis ( J:76608 )

• excessive epidermal hyperkeratosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
photosensitive trichothiodystrophy		DOID:2960		J:76608
xeroderma pigmentosum group A		DOID:0110843	OMIM:278700	J:76608

Genotype
MGI:3836475

cx8

• Allelic Composition: Ercc2^{tm2(ERCC2)Jhjh}/Ercc2^{tm2(ERCC2)Jhjh}; Ercc3^tm2Jhjh/Ercc3^tm2Jhjh
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:145759 )

• mice die within 2 days of birth

cellular

increased cellular sensitivity to gamma-irradiation ( J:145759 )

increased cellular sensitivity to oxidative stress ( J:145759 )

• mouse embryonic fibroblasts exhibit increased sensitivity to oxidative stress induced by paraquat treatment compared to similarly treated wild-type cells

increased cellular sensitivity to ultraviolet irradiation ( J:145759 )

• mouse embryonic fibroblasts exhibit slightly increased UV sensitivity compared to cells homozygous for either allele

growth/size/body

postnatal growth retardation ( J:145759 )

• mice fail to grow after birth despite nursing normally